Transactivation of C-Reactive Protein by IL-6 Requires Synergistic Interaction of CCAAT/Enhancer Binding Protein β (C/EBPβ) and Rel p50
| العنوان: | Transactivation of C-Reactive Protein by IL-6 Requires Synergistic Interaction of CCAAT/Enhancer Binding Protein β (C/EBPβ) and Rel p50 |
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| المؤلفون: | Hyunjoo Cha-Molstad, Irving Kushner, Alok Agrawal, David Samols |
| المصدر: | The Journal of Immunology. 166:2378-2384 |
| بيانات النشر: | The American Association of Immunologists, 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | Transcriptional Activation, Immunology, Biology, Transfection, Transactivation, Genes, Reporter, Enhancer binding, Consensus Sequence, Tumor Cells, Cultured, Humans, Immunology and Allergy, Luciferase, Binding site, Luciferases, Promoter Regions, Genetic, Transcription factor, Cell Nucleus, Binding Sites, Ccaat-enhancer-binding proteins, Interleukin-6, CCAAT-Enhancer-Binding Protein-beta, NF-kappa B, NF-kappa B p50 Subunit, Drug Synergism, Molecular biology, Proto-Oncogene Proteins c-rel, C-Reactive Protein, Electrophoresis, Polyacrylamide Gel, Dimerization |
| الوصف: | We have previously found that overexpression of the Rel protein p50 stimulated C-reactive protein (CRP) expression in Hep 3B cells and that p50 could bind to a nonconsensus κB site overlapping the CCAAT/enhancer binding protein (C/EBP) binding site centered at position −53 on the CRP promoter. Accordingly, we employed EMSA to investigate possible cooperation between p50 and C/EBP proteins using an oligonucleotide probe (−63/−41) derived from the CRP promoter and containing both C/EBP and p50 binding sites. Abs to p50, but not to p65, decreased formation of C/EBPβ-containing complexes in nuclei of IL-6-treated cells, indicating that ternary complexes containing C/EBPβ and p50 are formed on the CRP promoter. Depletion of free Rel proteins by pretreatment of nuclear extracts with a κB consensus oligonucleotide markedly decreased formation of C/EBP complexes, indicating that Rel proteins are required for formation of such complexes. Overexpression of p50 in transient cotransfection studies using the proximal CRP promoter (−125/+9) linked to a luciferase reporter caused a 3-fold increase of luciferase activity, while C/EBPβ overexpression caused an 18-fold increase; simultaneous overexpression of both transcription factors increased luciferase activity ∼600-fold. Mutation of either the C/EBP binding site or the p50 binding site drastically reduced the effects of overexpressed transcription factors. Taken together, our findings indicate that binding of Rel p50 to the nonconsensus κB site enhances and stabilizes binding of C/EBPβ to the CRP promoter and that binding of both C/EBPβ and p50 to their overlapping cognate sites is required for induction of CRP expression by IL-6. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d92258d4de491ef0e01199f2feccad8Test https://doi.org/10.4049/jimmunol.166.4.2378Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8d92258d4de491ef0e01199f2feccad8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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